Allopurinol May Slow Progression of Renal Disease in Patients With CKD

Laurie Barclay, MD

September 18, 2010

June 10, 2010 — Allopurinol may slow progression of renal disease in patients with chronic kidney disease (CKD), according to the results of a prospective, randomized trial published online June 10 in the Clinical Journal of the American Society of Nephrology.

"Hyperuricemia is associated with hypertension, inflammation, renal disease progression, and cardiovascular disease," write Marian Goicoechea, MD, from Hospital General Universitario Gregorio Marañón in Madrid, Spain, and colleagues. "However, no data are available regarding the effect of allopurinol in patients with chronic kidney disease."

Of 113 patients with estimated glomerular filtration rate (eGFR) levels lower than 60 mL/minute, 57 were randomly assigned to receive allopurinol 100 mg/day, and 56 to continue their usual therapy. To determine renal disease progression, cardiovascular events, and hospitalizations from any cause, clinical, biochemical, and inflammatory parameters were measured at baseline and at 6, 12, and 24 months of treatment.

Participants treated with allopurinol had significantly decreased serum uric acid and C-reactive protein levels. After 24 months, eGFR decreased 3.3 ± 1.2 mL/minute per 1.73 m2 in the control group, whereas it increased 1.3 ± 1.3 mL/minute per 1.73 m2 in the allopurinol group. Independent of age, sex, diabetes, C-reactive protein, albuminuria, and use of renin-angiotensin system blockers, allopurinol treatment was associated with slower progression of renal disease.

Cardiovascular events occurred in 22 patients after a mean follow-up time of 23.4 ± 7.8 months. Factors associated with increased cardiovascular risk were diabetes mellitus, previous coronary heart disease, and C-reactive protein levels. Compared with standard treatment, allopurinol treatment was associated with a 71% reduction in cardiovascular risk. Twenty-two patients from the control group and 12 from the allopurinol group were hospitalized during the course of the trial (P = .032). Based on a Cox regression model that included age, eGFR, presence of diabetes mellitus and coronary disease, this translates into a 62% reduced risk of hospitalization in those who took allopurinol (hazards ratio [HR], 0.378; 95% confidence interval, 0.154 - 0.927; P = .033).

"Allopurinol decreases C-reactive protein and slows down the progression of renal disease in patients with chronic kidney disease," the study authors write. "In addition, allopurinol reduces cardiovascular and hospitalization risk in these subjects."

Limitations of this study include lack of double-blinding, lack of dietary control or analysis, and concomitant use of statins, antiplatelet, and renin-angiotensin-aldosterone system blocker drugs.

"These results have to be confirmed in larger prospective trials and are the basis for a hypothesis that still needs to be tested," the study authors conclude.

The study authors have disclosed no relevant financial relationships.

Clin J Am Soc Nephrol. Published online June 10, 2010.

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